It is known that classic antihistamines, such as mepyramine, are capable of antagonizing some effects of histamine mediated by H.sub.1 -receptors. However, these compounds have no effect on gastric acid secretion which is instead affected by other antihistaminic agents defined by Black et al. (Nature 236, 385, 1972) as histamine H.sub.2 -receptor antagonists. This has indicated that another kind of receptors (H.sub.2) already recognized by Ash and Shild (Brit. J. Pharmacol. Chem. Ther., 27, 427-439, 1966) is involved in the gastric secretory response which is not blocked by the conventional antihistamines of the H.sub.1 -type.
Examples of H.sub.2 -receptor antagonists capable of antagonizing gastric acid secretion include burimamide, metiamide, and cimetidine. The clinical efficacy of the latter as a gastric antisecretory agent stimulated a search for agents with higher potency, longer duration of action, and lesser side effects.
Recently, new H.sub.2 -antagonists such as ranitidine (Bradshaw et al., Brit. J. Pharmacol. 66, 464P, 1979), tiotidine (P. O. Jellin, Life Sci. 25, 2001, 1979) and BL 6341 (Cavanagh et al., Fed. Proc., 40, 2652, 1981) have been described.
In a structural sense these compounds resemble cimetidine, since they contain a substituted heterocycle joined by a methylthioethyl side chain to a "urea equivalent" neutral polar group.
In copending U.S. applications Ser. No. 322,903, filed Nov. 19, 1981, now U.S. Pat. No. 4,386,099, and 465,572, filed Feb. 10, 1983, now U.S. Pat. No. 4,548,944, we have described new classes of histamine H.sub.2 -antagonists, namely heterocyclyl-phenyl-formamidines, which are potent H.sub.2 -blockers and active antagonists of gastric acid secretion. These compounds do not resemble the so far known H.sub.2 -antagonists, such as cimetidine, ranitidine, etc., and are characterized by a phenylformamidine grouping bearing variously substituted heterocyclic rings.